This proposal is concerned with the molecular mechanisms that regulate the synthesis and degradation of membrane lipids in bacteria. The metabolism of two vitamins, lipoic acid and biotin, that are related to fatty acid synthesis are also studied. The general approaches are to use genetics, biochemistry and molecular biology to unravel these mechanisms and determine how these pathways are regulated. The mechanisms of fatty acid synthesis are highly conserved throughout biology thus giving these studies general applicability. However, in the case of fatty acid synthesis the details of the pathways differ sufficiently from those of mammals that specific inhibitors of the bacterial enzymes have been found. Therefore, bacterial fatty acid synthetic enzymes are excellent targets for new antibiotics. It should be noted that a group of protozoan parasites including those causing malaria and toxoplasmosis have essential fatty acid enzymes which are close homologues to the bacterial proteins and thus new antibiotics may prove effective versus these diseases. The same may be true of biotin synthesis. PUBLIC HEALTH RELEVANCE: Fatty acids are a major component of the membrane that separated the inside of bacterial cells from the external environment. This proposal studies how these acids are made and provides a basis for antibiotics that kill bacteria by blocking synthesis of fatty acids and hence bacterial cell growth.